Imaging of cortical excitability with transcranial magnetic stimulation and electroencephalography in de novo Parkinsonian patients

Parkinson’s disease (PD) is the second most frequent neurodegenerative disorder. Unfortunately, there is no cure for PD and no neuroprotective treatment and about 95% of patients will become demented within 25 years after the diagnosis. The presentation and evolution of PD is highly heterogeneous between patients : different subtypes of the disease have been described, based on motor signs (for example, tremor-dominant or rigid-bradykinetic types) (Selikhova et al., 2009) and, more recently, on non-motor signs (cognitive or neocortical, autonomic and limbic subtypes) (Marras and Chaudhuri, 2016). Some PD phenotypes, namely the bradykinetic-rigid and neocortical forms, are more at risk of having a more severe and progressive course of the disease. However, although cognitive deficits are very frequent in old patients (Aarsland et al., 2007), in younger patients it is difficult to predict whether they will develop early cognitive disturbances, despite the availability of some biomarkers that are linked to higher risk of dementia (Svenningsson et al., 2012). Hence, subtyping PD patients at an early disease stage to predict the evolution to dementia is a useful strategy for personalizing patients’ management, and for guiding research on new medical approaches, including early use of neuroprotective therapies (Moro et al., 2016). In this proposal, we assume that in patients with a PD subtype characterized by prevalent cognitive issues, the impairment of cortical excitability in the fronto-parietal networks (Gratwicke et al., 2015) would be a new biomarker already detectable at an early disease stage. We will study the cortical excitability using innovative methodologies for brain stimulation that we recently developed. These are based on the concepts of functional cytoarchitectony (Harquel et al., 2016) and functional tractography (David et al., 2013), probing local and large scale neuronal communication with cortical stimulation, respectively.